Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Late-Onset of Acute Severe Ulcerative Colitis: Clinical Case.

Ulcerative colitis (UC) in adult age requires more careful examination because more often it turns out to be a complication related to the precancer condition. The onset of colitis in older age is predicted to follow a more aggressive clinical course and requires more frequent hospitalizations and steroids prescription in contrast to its onset in young patients. Even as this remains unclear, we present here a clinical case of late onset of acute severe UC to represent interesting clinical peculiarities and response to the therapy. Patient P., a 57-year-old male complained of 8 days of bloody diarrhea and lower abdominal pain. He reported having up to 3-5 urgent stool per day and 3-4 stool per night weight loss with dehydration. Stool culture was negative for infection, but fecal leukocytes were present. Flexible colonoscopy and biopsies were performed, which showed friable and erythematous mucosa with erosions and ulcers in a diffuse circumferential distribution from the anal verge to the cecum. There were no pseudomembranes. Histological evaluation revealed acute inflammation without architectural distortion consistent with either acute infectious colitis or new inflammatory bowel disease, favoring UC. Treatment for presumed UC is initiated with mesalazine 8 g daily: 4 g orally, 4 g per rectum and prednisone at 40 mg orally daily. After 48 h, stool frequency was 12 times per day (2 per night) with urgency, and blood was seen in stool occasionally. Intravenous steroids were prescribed - 16 mg of dexamethasone. After 48 h, stool frequency reduced to 8 per day, 1-2 per night, with traces of blood in stool and general well-being was increased. But after 14 days, the condition did not change significantly. Infliximab 5 mg/kg was administered and after the first infusion, stool frequency reduced to 4 times per day without urgency and night diarrhea. Azathioprine 100 mg per day was prescribed after steroid (prednisone) withdrawal. But after the third infusion of infliximab, the patient felt pain along the intercostal nerves along with skin redness and itching. Herpes zoster virus infection was diagnosed. Famciclovir 750 mg per day was prescribed, azathioprine was stopped, infusions of infliximab were continued and after 12 months, patient was started on a monotherapy of infliximab 1 time per 8 weeks and he had stable remission.

Mucosal barrier in ulcerative colitis and Crohn's disease.

Background. The mucus layer in the gastrointestinal tract plays important role in host innate defense, regulation of secretion, and absorption processes, maintaining colonization resistance, which composes the integrity of protective mucus barrier in the large intestine. Investigations of mucin expression in the colon mucosa can improve the understanding of protective function of mucosal barrier in ulcerative colitis (UC) and Crohn's disease (CD). Materials and Methods. 77 patients with UC and CD were examined. Histological analysis of colon mucosa was done by standard method (haematoxylin-eosin, alcian blue at pH 1.0 and 2.5 to determine sulfated and nonsulfated glycosaminoglycans and glycoproteins, and goblet cells). To characterize the mucus production the PAS-reaction was performed. Immunohistochemistry was performed using monoclonal mouse antibodies raised against MUC2, MUC3, MUC4, and TFF3 (USBiological, USA). Results. The moderate expression of MUC2 and MUC3 (50.0% and 32.1%, P = 0.03) and high expression of MUC4 and TFF3 in the colon mucosa were observed in all patients with CD. The intensive labeling of MUC4 and TFF3 occurred more often (42.9% and 57.1%, P = 0.03) in patients with CD. The level of expression of secretory MUC2 and transmembrane MUC3 and MUC4 in all patients with UC was low, up to its complete absence (59.2% and 53.1% cases, P = 0.05). TFF3 expression had high and medium staining intensity in patients with UC. Conclusions. Different types of mucins synthesis, secretion, and expression were found in patients with UC and CD. The expression of mucin MUC2, MUC3, MUC4, and TFF3 correlated with the activity of disease and the extent of the inflammatory process in the large intestine. The most pronounced alteration of mucins expression was observed in patients with severe UC and CD.

Joint extraintestinal manifestations in ulcerative colitis.

An extraintestinal manifestation (EIM) very often occurs in ulcerative colitis (UC) patients. EIM modifies the natural course of UC and decreases the quality of life in these patients. The aim of this study was to analyze clinical and laboratory findings in UC patients with joint EIM. 319 UC patients were examined. Among them were 131 (41.1%) patients with distal UC, 102 (32.0%) suffered from left-sided UC and 86 (26.9%) had pancolitis. 95 (29.8%) UC patients had joint EIM. Arthritis correlated with extensive forms of UC and was more often determined in patients with left-sided UC and pancolitis. Arthralgia was a prevalent symptom of joint EIM in patients with distal UC. Colon microbiocenosis and the mucosal barrier in UC patients were analyzed. The cytokine status with privileged cytokine profile changes was investigated. In all UC patients, dysbiosis with a decreasing quantity of bifidobacteria, lactobacilli and Escherichia coli was found, but an increase of facultative flora was also found. At the same time, an association of facultative flora in UC patients with arthritis was observed. In these patients, Staphylococcus, Klebsiella and Proteus were found more often in stool cultures. These associations correlated with a modification of the colonocytes' cell receptor maturity of mucus, a condition with a decreased staining intensity by lectins. A cytokine imbalance with an increase of proinflammatory and a decrease of anti-inflammatory cytokines was found in all UC patients. The privileged cytokine profile changes in UC patients with joint EIM were analyzed. Maximal increases of IL-1 and TNF with decreases of IL-10 in plasma in patients with joint EIM were observed.